[Clinical efficacy of combined therapy in children with stage 4 neuroblastoma]. / 儿童4期神经母细胞瘤联合治疗的临床疗效观察.

OBJECTIVES: To study the early clinical efficacy of combined therapy of stage 4 neuroblastoma. METHODS: A retrospective analysis was performed on the medical data and follow-up data of 14 children with stage 4 neuroblastoma who were diagnosed in Hong Kong University-Shenzhen Hospital from January 2016 to June 2021. RESULTS: The median age of onset was 3 years and 7.5 months in these 14 children. Among these children, 9 had positive results of bone marrow biopsy, 4 had N-Myc gene amplification, 13 had an increase in neuron-specific enolase, and 7 had an increase in vanilmandelic acid in urine. Based on the results of pathological examination, differentiated type was observed in 6 children, undifferentiated type in one child, mixed type, in one child and poorly differentiated type in 6 children. Of all the children, 10 received chemotherapy with the N7 regimen (including 2 children receiving arsenic trioxide in addition) and 4 received chemotherapy with the Rapid COJEC regimen. Thirteen children underwent surgery, 14 received hematopoietic stem cell transplantation, and 10 received radiotherapy. A total of 8 children received Ch14.18/CHO immunotherapy, among whom 1 child discontinued due to anaphylactic shock during immunotherapy, and the other 7 children completed Ch14.18/CHO treatment without serious adverse events, among whom 1 child was treated with Lu177 Dotatate 3 times after recurrence and is still undergoing chemotherapy at present. The median follow-up time was 45 months for all the 14 children. Four children experienced recurrence within 2 years, and the 2-year overall survival rate was 100%; 4 children experienced recurrence within 3 years, and 7 achieved disease-free survival within 3 years. CONCLUSIONS: Multidisciplinary combined therapy is recommended for children with stage 4 neuroblastoma and can help them achieve better survival and prognosis.

Involvement of c-Myc in low dose radiation-induced senescence enhanced migration and invasion of unirradiated cancer cells.

Ionizing radiation is known to cause cell apoptosis at high dose range, but little is known about the cellular response to low dose radiation. In this study, we found that conditioned medium harvested from WI-38 lung fibroblasts and H1299 lung adenocarcinoma cells exposed to 0.1Gy to 1Gy could enhance the migration and invasion of unirradiated H1299 cells in both 2D and 3D culturing circumstances. Low dose radiation did not induce apoptosis, but induced senescence in irradiated cells. We next examined the expression of immediately early genes including c-Myc and K-Ras. Although both genes could be up-regulated by low dose radiation, induction of c-Myc was more specific to low dose range (0.5Gy) at transcriptional and translational levels. Knockdown of c-Myc by shRNA could repress the senescence induced by low dose radiation. The conditioned medium of irradiated cells induced migration of unirradiated cells was also repressed by knockdown of c-Myc. The c-Myc inhibitor 10058-F4 could suppress low dose radiation induced cell senescence, and the conditioned medium harvested from irradiated cells pretreated with 10058-F4 also lost the ability to enhance the migration of unirradiated cells. The cytokine array analysis revealed that immunosuppressive monocyte chemoattractant protein-1 increased by low dose radiation could be repressed by 10058-F4. We also showed that 10058-F4 could suppress low dose radiation induced tumor progression in a xenograft tumor model. Taken together, current data suggest that -Myc is involved in low dose radiation induced cell senescence and potent bystander effect to increase the motility of unirradiated cells.

Association between the HOTAIR Polymorphism and Susceptibility to Lead Poisoning in a Chinese Population.

This study explored the association between the lncRNA HOTAIR polymorphism and susceptibility to lead poisoning in a Chinese population. We speculated that lead poisoning caused elevated levels of oxidative stress, which, in turn, activate the HOTAIR gene to cause apoptosis. Three lncRNA HOTAIR tagSNPs (rs7958904, rs4759314, and rs874945) were genotyped by TaqMan genotyping technology in 113 lead-sensitive and 113 lead-resistant Chinese workers exposed to lead. Rs7958904 was significantly associated with susceptibility to lead poisoning (P = 0.047). The rs7958904 G allele had a protective effect compared with the C allele and reduced the risk of lead poisoning (P = 0.016). Rs7958904 may act as a potential biomarker for predicting the risk of lead poisoning and distinguishing lead-sensitive individuals from lead-resistant individuals.

Acute Pesticide Poisoning in Jiangsu Province, China, from 2006 to 2015.

This study aimed to investigate the characteristics of pesticide poisoning in Jiangsu Province, China, and to provide a scientific basis for developing effective interventional measures and preventive strategies. From 2006 to 2015, a total of 35,308 cases of pesticide poisoning were reported in Jiangsu Province. Non-occupational poisoning accounted for 73.79% of all poisoning cases. A comparison of the data collected before (2006) and after (2015) this study showed a decrease in non-occupational pesticide poisoning. Pesticide poisoning showed an age central tendency of 30 to 44 years, area central tendency for northern Jiangsu, and seasonal central tendency of occupational pesticide poisoning in autumn. Pesticide poisoning remains a major health concern in China. Government agencies together with scientists should focus their efforts on the prevention of potential threats to vulnerable groups such as the elderly, women, and children.

Association between MDM2-SNP309 and p53R72P polymorphisms and the risk of bladder cancer in the Mongolian population.

The current study aims to investigate whether MDM2-SNP309 and p53R72P polymorphisms were associated with the risk of bladder cancer in Mongolian populations. These polymorphisms were evaluated in 79 controls and 63 bladder cancer cases using a PCR-restriction fragment length polymorphism assay, followed by analysis using multivariate logistic regression model and the Kaplan-Meier model to determine the odds ratio (OR) and age at onset of bladder cancer, respectively. The results revealed that the homozygous (G/G) genotype of MDM2-SNP309 increased the risk of bladder cancer compared to the wild-type (T/T) genotype [OR=1.629; 95% confidence interval (CI)=0.622-4.266] among Mongolians. On the other hand, the homozygous (P/P) genotype of p53R72P tended to protect the population from bladder cancer compared with the wild-type (R/R) genotype (OR=0.445; 95% CI=0.1727-2.147). It also showed that G/G genotype of MDM2-SNP309 increased the risk of bladder cancer when combined with the R/R genotype of p53R72P (OR=3.355; 95% CI=0.3914-28.766). Stratification by smoking and history of chronic urinary tract diseases tended towards increasing the risk association of the G/G (OR=2.3704; 95% CI=0.4308-3.044) and T/G genotypes (OR=5; 95% CI=0.8442-30.4088) of MDM2-SNP309 with bladder cancer, respectively. The protective role of P/P of p53R72P remained following stratification. MDM2-SNP309 and p53R72P were not involved in early age onset of bladder cancer in Mongolian patients. Taken together, MDM2-SNP309 and p53R72P had no significant association with bladder cancer in Mongolian patients. The two SNPs were also not able to predict early age at onset of bladder cancer.

Association between Plasma Metal Levels and Diabetes Risk: a Case-control Study in China.

OBJECTIVE: Many metals, some of which have been classified as environmental endocrine disruptors, are used extensively in everyday consumer products and are ubiquitous in our living environment. In the present study, we aimed to explore the associations between the prevalence risk of type 2 diabetes and plasma levels of 20 trace elements as well as those of heavy metals in a Han Chinese population. METHODS: We conducted a case-control study to investigate the associations between plasma concentrations of 20 metals and diabetes in Jiangsu province. A total of 122 newly diagnosed cases of type 2 diabetes and 429 matched controls were recruited from community physical examinations in Suzhou City of Jiangsu Province. Plasma metal levels were measured by inductively-coupled plasma mass spectrometry. RESULTS: After adjusting for confounders, plasma vanadium, chromium, manganese, copper, zinc, arsenic, selenium, strontium, palladium, cadmium, cesium, and barium were associated with diabetes risk (P < 0.05). The adjusted OR increased with increasing concentration of vanadium, manganese, copper, zinc, and cesium. CONCLUSION: Many metals, including manganese, copper, zinc, arsenic, selenium, and cadmium in plasma, are associated with the morbidity of diabetes. Monitoring of environmental metal levels and further studies are urgently needed.

Combining fisetin and ionizing radiation suppresses the growth of mammalian colorectal cancers in xenograft tumor models.

Fisetin (3,7,3',4'-tetrahydroxyflavone), which belongs to the flavonoid group of polyphenols and is found in a wide range of plants, has been reported to exhibit a number of biological activities in human cancer cells, including antioxidant, anti-inflammatory, antiangiogenic, anti-invasive and antiproliferative effects. Although previous in vitro studies have shown that fisetin treatment increases the apoptotic rate and enhances the radiosensitivity of human colorectal cancer cells, the in vivo effects of fisetin on tumor growth remain unclear. In the present study a murine xenograft tumor model was employed to investigate the therapeutic effects of fisetin in combination with radiation on CT-26 colon cancer cells and human HCT116 colorectal cancer cells. This revealed that intratumoral injection of fisetin significantly suppressed the growth of CT-26 tumors compared with the untreated control group, but had little effect on the growth of HCT116 tumors. However, fisetin in combination with 2-Gy radiation enhanced tumor suppressor activity in murine colon and human colorectal xenograft tumors, as compared with 2-Gy fractionated radiation administered alone for 5 days and fisetin alone. Interestingly, fisetin downregulated the expression of the oncoprotein securin in a p53-independent manner. However, securin-null HCT116 tumors showed only moderate sensitivity to fisetin treatment, and the combination of fisetin and radiation did not significantly suppress securin-null HCT116 tumor growth compared with normal HCT116 tumors. Therefore, the role of securin in mediating the effect of fisetin on colorectal cancer growth warrants further investigation. In conclusion, the results of the current study provide important preclinical data for evaluating the efficacy of fisetin and radiation combination treatment as an adjuvant chemoradiotherapy for human colorectal cancers.

Analysis of plasma microRNA expression profiles in male textile workers with noise-induced hearing loss.

BACKGROUND: Circulating microRNAs (miRNAs) have attracted interests as non-invasive biomarkers of physiological and pathological conditions, which may be applied in noise-induced hearing loss (NIHL). However, no epidemiology studies have yet examined the potential effects of NIHL or noise exposure on miRNA expression profiles. OBJECTIVES: We sought to identify permanent NIHL-related miRNAs and to predict the biological functions of the putative genes encoding the indicated miRNAs. METHODS: In the discovery stage, we used a microarray assay to detect the miRNA expression profiles between pooled plasma samples from 10 noise-exposed individuals with normal hearing and 10 NIHL patients. In addition, we conducted a preliminary validation of six candidate miRNAs in the same 20 workers. Subsequently, three miRNAs were selected for expanded validation in 23 non-exposed individuals with normal hearing and 46 noise-exposed textile workers which including 23 noise-exposed workers with normal hearing and 23 NIHL patients. Moreover, we predicted the biological functions of the putative target genes using a Gene Ontology (GO) function enrichment analysis. RESULTS: In the discovery stage, compared with the noise exposures with normal hearing, 73 miRNAs demonstrated at least a 1.5-fold differential expression in the NIHL patients. In the preliminary validation, compared with the noise exposures, the plasma levels of miR-16-5p, miR-24-3p, miR-185-5p and miR-451a were all upregulated (P < 0.001) in the NIHL patients. In the expanded validation stage, compared with the non-exposures, the plasma levels of miR-24, miR-185-5p and miR-451a were all significantly downregulated (P < 0.001) in the exposures. And compared with the noise exposures, the plasma levels of miR-185-5p and miR-451a were slightly elevated (P < 0.001) in the NIHL patients, which were consistent with the results of preliminary validation and microarray analysis. CONCLUSION: The two indicated plasma miRNAs may be biomarkers of indicating responses to noise exposure. However, further studies are necessary to prove the causal association between miRNAs changes and noise exposure, and to determine whether these two miRNAs are clear biomarkers to noise exposure.